Persistent organic pollutants (POPs) are ubiquitous in the ecosystem and may be causing adverse health effects at background levels of exposure, via diet. The most important POPs are DDE (the major metabolite of the insecticide DDT), polychlorinated biphenyls (PCBs), and dioxin (tetrachlorodibenzo-p-dioxin, or TCDD). DDT is still used in about 25 countries for control of disease vectors, especially for malaria, under the assumption that there are no adverse human health effects. My recent findings are that higher maternal serum DDE level is associated with increased risks of preterm birth and fetal loss. If these findings are replicated, they could affect vector control policies in other countries and help reduce the global burden of this persistent toxic substance. PCBs are resistant to chemical and biological breakdown and this contributed to their widespread commercial use in a variety of applications. Even though the manufacture of PCBs has been banned worldwide, they persist in measurable amounts in nearly everyone in developed countries. Animal and human data suggest that PCBs interfere with thyroid hormone metabolism and are neurotoxic even at levels found in background-exposed humans. Epidemiologic data on health effects guide advisories regarding fish consumption and are needed to evaluate whether further preventive measures are in order. My research in this area has addressed potential thyrotoxicity, neurodevelopmental toxicity, and more recently has uncovered an association with diabetes. TCDD is created inadvertently as a byproduct of chemical manufacturing or disposal. TCDD has been considered one of the most potent toxic substances known. Measurable amounts of TCDD are in virtually everyone in the United States. Of particular interest is that recent animal and human data suggest that TCDD interferes with glucose metabolism, even at background levels of exposure. The Collaborative Perinatal Project (CPP) was a prospective study of the cause of neurologic disorders and other conditions in U.S. children. Pregnant women were enrolled when they presented for prenatal care. The CPP mothers were urban dwellers, and had a median socioeconomic index 7% below the U.S. value. The mothers? nonfasting blood was collected approximately every 8 weeks, at delivery, and 6 weeks postpartum. The children were systematically assessed for the presence of neurodevelopmental defects and other outcomes through age 7 years. Summary: CPP Specimens. In two studies using CPP specimens, we measured sodium concentration to assess desiccation. Prenatal PCB Exposure: We examined the association between fetal loss in previous pregnancies and DDE levels that were in a range where effects had been seen in two other studies. Complete data were available for 2,380 subjects, of whom 361 were born preterm and 221 were small-for-gestational age. We examined maternal DDE level during pregnancy in relation to adjusted odds of cryptorchidism, hypospadias, and polythelia [extra nipples] among their male offspring. We evaluated prenatal PCB exposure in relation to cognitive test scores (IQ) on the Wechsler Intelligence Scale for Children (WISC) at age 7 years. Third trimester serum was analyzed for PCBs in 1997-1999 for 730 women selected at random and for an additional 153 women whose children had either a low or high IQ score. The PCB-IQ association was examined while adjusting for study center, maternal age, race, serum lipids, parity, socioeconomic status, smoking, and education, and child?s gender, breast feeding, and other factors. Other exposure: The relations between concentrations of plasma DDE and several serum androgens were examined in 137 North Carolina black male farmers. Most had farmed about 30 years and 27% reported having used DDT. We studied indices of hematologic function and exposure to TCDD in Vietnam War veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of herbicides that were contaminated with TCDD. A comparison group of Air Force veterans who served in Southeast Asia during the same period and who were not involved with spraying herbicides served as referents. We studied serum TCDD level in relation to red blood cell count, white blood cell count, hemoglobin, hematocrit, mean corpuscular volume, platelet count, and erythrocyte sedimentation rate at each of four physical examinations over 10 years. We measured TCDD serum level in 1987 or 1992, extrapolated the result to the time of service in Vietnam, and assigned each veteran to one of four exposure categories: Comparison and three Ranch Hand categories (Background, Low, High). Reviews and meta-analyses: We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. We found that a) the distribution of PCB exposure in the majority of studies overlapped substantially, b) exposure levels in the Faroe Islands study were about 3-4 times higher than in most other studies, and c) the exposure levels in the two recent U.S. studies were about one third of those in the four earlier U.S. studies or recent Dutch, German, and Northern Quebec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. We reviewed the effects of mean exposure experienced by the general public, resulting primarily from normal die, and not from unusual circumstances of occupation, accident, or local contamination. We also reviewed selected studies of populations with high consumption of fish or marine mammals. To facilitate interpretation of experimental data on polychlorinated biphenyl (PCB) toxicity, we determined whether the PCB doses used in animal experiments result in tissue levels that were comparable to those observed in background-exposed humans. We identified 8 animal studies in which PCB tissue levels had been measured after oral dosing for more than one week, and compared the concentrations to those observed in 9 representative studies of background-exposed humans. Several recent animal studies have examined the effects of low-level PCBs (<0.05 mg/kg/d) in several species, with resulting tissue levels comparable to those in humans. If such low-dose PCB studies continue to suggest adverse effects in animals this would strongly support the biologic plausibility that background-level PCB exposure in humans could have similar consequences. We considered the importance of assessing endocrine disruption in a large new birth cohort that has been proposed, the National Children's Study (NCS). We believe it is highly likely that excellent hypotheses about human endocrine disruption will arise, and that the NCS should be designed to accommodate as many such possibilities as is feasible. We reviewed the epidemiologic data that addressed whether environmental contaminants might cause type 1 or type 2 diabetes. For type 1 diabetes, higher intake of nitrates, nitrites, and N-nitroso compounds, and higher serum levels of polychlorinated biphenyls have been associated with increased risk. With respect to type 2 diabetes, data on arsenic and TCDD in relation to risk were suggestive of a direct association. The occupational data suggested that more data on exposure to N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful.